Calcium entry through
L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation
calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with
left ventricular dysfunction, and their combination with a
beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity.
Felodipine is a highly vascular selective
calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally.
Isradipine and
nicardipine are also vascularly selective
calcium entry blockers. Hemodynamic studies in patients with
hypertension,
coronary artery disease,
congestive heart failure, or in patients receiving beta-
adrenergic blockade, show that
felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore,
felodipine alone or when added to a
beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of
dihydropyridine calcium entry blockers in
hypertension and
angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant
left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with
heart failure indicate that
felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.